A New Molecule for Memory: It can Enhance, or Erase

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Taking the memory-erasing ability shown in the 2004 movie
"Eternal Sunshine of the Spotless Mind" a step further,
scientists have found a molecule that not only erases but also
augments and strengthens memories, months after the fact.

"If you take coffee or amphetamines that make the brain more
excitable, your initial
learning can be a little better, as any student would know,"
said researcher Todd Sacktor of SUNY Downstate Medical Center.
"What never had been done before was to be able to, after you
learn something, wait days to weeks later, and then do something
that would be able to enhance those previously stored memories."

Previous studies of memory-modulating compounds have mainly been
focused on treatment during periods of learning or remembering.
Sacktor's research has pinpointed a brain enzyme that plays an
integral role in the maintenance of long-term memory.

Where memories are made

Sacktor and co-researcher Yadin Dudai of the Weizmann Institute
of Science in Israel conditioned rats to associate a taste with
feeling sick to their stomachs, much like humans after a
particularly nasty batch of food poisoning. This memory becomes
encoded in the brain and for months after the nauseating
experience the rats avoid any similar-tasting foods.

To change the rats' memories the researchers first trained them
to associate certain foods with bellyaches, then injected them
with a non-illness-inducing virus made specifically to express a
memory-altering enzyme. The enzyme is called protein kinase M
zeta, or PKMzeta for short. The virus made either the working
version of the protein or a mutant form that blocked the activity
of even the naturally expressed protein.

They saw that the increased enzyme levels enhanced the rat's
ability to remember, while the activity-blocking mutant
wiped out the memory.

PKMzeta appears to work in a different way than other memory
enhancers, which seem to
boost our brain's natural means of consolidating, or turning
everyday experiences into lasting memories. But scientists didn't
know the mechanism that keeps these long-term memories accessible
after consolidation.

Dudai and his team believe that PKMzeta is integral in this
"sustainability" of memories. "People used to think that memory
maintenance is a passive process, that there wasn't much to put
into it, that you
just change the wiring," Karim Nader, a researcher at McGill
University in Canada who wasn't involved in the study, said.
"This suggests that the mechanisms of memory maintenance are
actively maintained, and even manipulated."

Next memory-boosting drug?

In the future, it's possible this protein could be the target of
memory-changing drugs. Such drugs could treat
Alzheimer's patients, by strengthening their memories, or
individuals with post-traumatic stress disorder (PTSD) as well as
phobia patients, by decreasing their memory of fear-inducing
moments. Different memories could be targeted by changing PKMzeta
in different brain areas.

"There are other molecules that have been implicated in memory
maintenance," David Glanzman of UCLA, who wasn't involved in the
study, told LiveScience. "But it's clear that PKMzeta is a sort
of master molecule."

Even after having their memory of the nauseating taste wiped out,
the rats could still relearn to dislike it, similar to (spoiler
alert!) the reunion of the “Spotless Mind” characters after their
first memory wipe. "That area of the brain is still capable of
learning new things," Dudai said."We didn't damage it to such a
degree that we interfered with this ability."

This study will be published in the March 4 issue of the journal
Science.